Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: SDHA

Gene summary for SDHA

Gene summary.

Gene information	Species	Human
	Gene symbol	SDHA
	Gene ID	6389
	Gene name	succinate dehydrogenase complex flavoprotein subunit A
	Gene Alias	CMD1GG
	Cytomap	5p15.33
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	P31040

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
6389	SDHA	HTA11_2487_2000001011	Human	Colorectum	SER	3.40e-11	6.37e-01	-0.1808
6389	SDHA	HTA11_1938_2000001011	Human	Colorectum	AD	3.27e-11	6.92e-01	-0.0811
6389	SDHA	HTA11_78_2000001011	Human	Colorectum	AD	2.89e-08	6.56e-01	-0.1088
6389	SDHA	HTA11_347_2000001011	Human	Colorectum	AD	3.30e-33	9.08e-01	-0.1954
6389	SDHA	HTA11_411_2000001011	Human	Colorectum	SER	3.10e-06	1.06e+00	-0.2602
6389	SDHA	HTA11_83_2000001011	Human	Colorectum	SER	3.27e-07	7.98e-01	-0.1526
6389	SDHA	HTA11_696_2000001011	Human	Colorectum	AD	2.49e-11	6.72e-01	-0.1464
6389	SDHA	HTA11_866_2000001011	Human	Colorectum	AD	2.03e-04	4.56e-01	-0.1001
6389	SDHA	HTA11_1391_2000001011	Human	Colorectum	AD	7.19e-12	8.51e-01	-0.059
6389	SDHA	HTA11_2992_2000001011	Human	Colorectum	SER	7.51e-07	7.92e-01	-0.1706
6389	SDHA	HTA11_5212_2000001011	Human	Colorectum	AD	1.94e-02	6.41e-01	-0.2061
6389	SDHA	HTA11_5216_2000001011	Human	Colorectum	SER	1.20e-02	6.53e-01	-0.1462
6389	SDHA	HTA11_546_2000001011	Human	Colorectum	AD	1.94e-03	5.54e-01	-0.0842
6389	SDHA	HTA11_866_3004761011	Human	Colorectum	AD	3.79e-04	4.14e-01	0.096
6389	SDHA	A002-C-010	Human	Colorectum	FAP	4.15e-02	-1.29e-01	0.242
6389	SDHA	A015-C-203	Human	Colorectum	FAP	5.90e-14	-2.63e-01	-0.1294
6389	SDHA	A002-C-201	Human	Colorectum	FAP	1.43e-05	-2.39e-01	0.0324
6389	SDHA	A002-C-203	Human	Colorectum	FAP	4.98e-03	-1.62e-01	0.2786
6389	SDHA	A001-C-119	Human	Colorectum	FAP	7.47e-05	-3.75e-01	-0.1557
6389	SDHA	A001-C-108	Human	Colorectum	FAP	1.80e-08	-2.02e-01	-0.0272

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0006119	Colorectum	AD	oxidative phosphorylation	83/3918	141/18723	7.95e-23	8.30e-20	83
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0022900	Colorectum	AD	electron transport chain	89/3918	175/18723	1.42e-18	8.91e-16	89
GO:0019646	Colorectum	AD	aerobic electron transport chain	53/3918	87/18723	5.58e-16	2.16e-13	53
GO:0042773	Colorectum	AD	ATP synthesis coupled electron transport	56/3918	95/18723	6.76e-16	2.22e-13	56
GO:0042775	Colorectum	AD	mitochondrial ATP synthesis coupled electron transport	56/3918	95/18723	6.76e-16	2.22e-13	56
GO:0022904	Colorectum	AD	respiratory electron transport chain	63/3918	114/18723	8.23e-16	2.45e-13	63
GO:0033108	Colorectum	AD	mitochondrial respiratory chain complex assembly	46/3918	93/18723	8.95e-10	6.91e-08	46
GO:0006099	Colorectum	AD	tricarboxylic acid cycle	19/3918	30/18723	5.82e-07	2.09e-05	19
GO:0030111	Colorectum	AD	regulation of Wnt signaling pathway	102/3918	328/18723	8.51e-06	2.03e-04	102
GO:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0016311	Colorectum	AD	dephosphorylation	123/3918	417/18723	1.84e-05	3.82e-04	123
GO:0019318	Colorectum	AD	hexose metabolic process	77/3918	237/18723	1.96e-05	4.01e-04	77
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0006470	Colorectum	AD	protein dephosphorylation	88/3918	281/18723	2.56e-05	4.89e-04	88
GO:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493237	Oral cavity	LP	Non-alcoholic fatty liver disease	101/2418	155/8465	1.53e-21	6.37e-20	4.10e-20	101
hsa0502037	Oral cavity	LP	Prion disease	149/2418	273/8465	4.88e-20	1.81e-18	1.16e-18	149
hsa0520838	Oral cavity	LP	Chemical carcinogenesis - reactive oxygen species	119/2418	223/8465	3.00e-15	8.32e-14	5.37e-14	119
hsa0019037	Oral cavity	LP	Oxidative phosphorylation	81/2418	134/8465	9.58e-15	2.45e-13	1.58e-13	81
hsa0541537	Oral cavity	LP	Diabetic cardiomyopathy	106/2418	203/8465	6.51e-13	1.36e-11	8.74e-12	106
hsa0120032	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0471438	Oral cavity	LP	Thermogenesis	105/2418	232/8465	3.14e-08	4.98e-07	3.21e-07	105
hsa0002032	Oral cavity	LP	Citrate cycle (TCA cycle)	22/2418	30/8465	4.66e-07	5.97e-06	3.85e-06	22
hsa0501262	Oral cavity	NEOLP	Parkinson disease	78/1112	266/8465	1.34e-12	1.06e-10	6.68e-11	78
hsa0520863	Oral cavity	NEOLP	Chemical carcinogenesis - reactive oxygen species	68/1112	223/8465	5.39e-12	2.86e-10	1.80e-10	68
hsa0501462	Oral cavity	NEOLP	Amyotrophic lateral sclerosis	95/1112	364/8465	8.76e-12	3.98e-10	2.50e-10	95
hsa0501062	Oral cavity	NEOLP	Alzheimer disease	97/1112	384/8465	3.97e-11	1.57e-09	9.89e-10	97
hsa0541562	Oral cavity	NEOLP	Diabetic cardiomyopathy	62/1112	203/8465	4.45e-11	1.57e-09	9.89e-10	62
hsa0493263	Oral cavity	NEOLP	Non-alcoholic fatty liver disease	51/1112	155/8465	1.26e-10	3.84e-09	2.41e-09	51
hsa0502262	Oral cavity	NEOLP	Pathways of neurodegeneration - multiple diseases	112/1112	476/8465	1.33e-10	3.84e-09	2.41e-09	112
hsa0502062	Oral cavity	NEOLP	Prion disease	73/1112	273/8465	7.94e-10	2.10e-08	1.32e-08	73
hsa0501662	Oral cavity	NEOLP	Huntington disease	75/1112	306/8465	2.92e-08	5.34e-07	3.36e-07	75
hsa0471462	Oral cavity	NEOLP	Thermogenesis	56/1112	232/8465	2.86e-06	2.75e-05	1.73e-05	56
hsa0501272	Oral cavity	NEOLP	Parkinson disease	78/1112	266/8465	1.34e-12	1.06e-10	6.68e-11	78
hsa0520873	Oral cavity	NEOLP	Chemical carcinogenesis - reactive oxygen species	68/1112	223/8465	5.39e-12	2.86e-10	1.80e-10	68

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

SDHA

SNV

Missense_Mutation

novel

c.145G>A

p.Asp49Asn

p.D49N

P31040

protein_coding

tolerated_low_confidence(0.27)

benign(0)

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SDHA

SNV

Missense_Mutation

rs370690436

c.1352G>A

p.Arg451His

p.R451H

P31040

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-BH-A0BW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

SDHA

insertion

Frame_Shift_Ins

novel

c.1029_1030insCCAAAGAACCAGACCTGTGTCTTCTCTT

p.Ser344ProfsTer26

p.S344Pfs*26

P31040

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SDHA

insertion

In_Frame_Ins

novel

c.1193_1194insATCCCAGCACTTTGGGAGGCTGAA

p.Glu398_Pro399insSerGlnHisPheGlyArgLeuLys

p.E398_P399insSQHFGRLK

P31040

protein_coding

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

SDHA

SNV

Missense_Mutation

rs375576259

c.442G>A

p.Ala148Thr

p.A148T

P31040

protein_coding

tolerated_low_confidence(0.47)

benign(0.057)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SDHA

SNV

Missense_Mutation

novel

c.1397C>T

p.Ala466Val

p.A466V

P31040

protein_coding

deleterious_low_confidence(0.01)

benign(0.069)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SDHA

SNV

Missense_Mutation

c.178N>T

p.His60Tyr

p.H60Y

P31040

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.993)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

SDHA

SNV

Missense_Mutation

c.1144N>C

p.Gly382Arg

p.G382R

P31040

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

SDHA

SNV

Missense_Mutation

rs199615452

c.251N>A

p.Gly84Glu

p.G84E

P31040

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SDHA

SNV

Missense_Mutation

c.485N>C

p.Arg162Thr

p.R162T

P31040

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-IR-A3LF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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